Abstract
Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics-and not changes in lesions or brain volume-were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.
Highlights
Relapsing-remitting multiple sclerosis (RRMS) is a chronic progressive disease that evolves through clinical relapses and subclinical inflammation and degeneration [1]
At baseline, no significant differences were observed between mean quantitative MRI (qMRI) metrics in NAWM, NAGM, and basal ganglia in patients vs controls
Our study shows that the combination of multiple qMRI metrics is sensitive to 2-year changes in brain pathology in a group of early-stage MS patients on therapy, suggesting a decrease in NAWM inflammation as well as repair processes in lesions
Summary
Relapsing-remitting multiple sclerosis (RRMS) is a chronic progressive disease that evolves through clinical relapses and subclinical inflammation and degeneration [1]. T2 rt is highly sensitive to free-water content, it is affected by the presence of macromolecules and iron. Both an accumulation of free water and a loss of macromolecules will increase T2 rt, while iron will decrease it [16]. The metrics obtained with MTI are very sensitive to variation of large molecular aggregates like lipids and proteins in myelin or cellular membranes [18, 19] so that they decrease when the amount of macromolecules decreases (i.e., in demyelination and/or cell loss) and/ or the free water increases (i.e., edema) [20]. Combining multiple qMRI techniques in a clinically compatible protocol is challenging (e.g., due to motion, scan time, reproducibility, etc.) but there are currently ongoing efforts toward fast and reproducible protocols applying combined and accelerated acquisitions [21,22,23], synthetic computation of qMRI metrics [22] and qMRI fingerprinting [24]
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